The differentiation and integration of the hippocampal dorsoventral axis are controlled by two nuclear receptor genes
- Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, China
- Guangzhou Laboratory/Bioland Laboratory, China
- CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Figures
Figure 1 with 1 supplement
Duplicated CA1 and CA3 domains are generated in the ventral hippocampus of RXCre/+; Nr2f2F/F mutant mice.
(A) The expression of NR2F1 (a, d, g, j, m) and NR2F2 (b, e, h, k, n) in coronal sections (a–f) and sagittal sections (g–o) of the hippocampus at postnatal month 1 (1M); representative western blots …
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Figure 1—source data 1
The Nissl staining results of the control and RXCre/+; Nr2f2F/F mutant mice at 1M (part 1); the expression of HuB and Ctip2 in the hippocampus of the control and RXCre/+; Nr2f2F/F mutant mice at 1M (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data1-v1.zip
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Figure 1—source data 2
The expression of NR2F1 and NR2F2 in coronal sections and sagittal sections of the mouse brain at 1M (part 1); the expression of HuB and Ctip2 in the hippocampus of the control and RXCre/+; Nr2f2F/F mutant mice at 1M (part 2).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data2-v1.zip
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Figure 1—source data 3
The expression of NR2F1 and NR2F2 in coronal sections and sagittal sections of the mouse brain at 1M (part 2).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data3-v1.zip
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Figure 1—source data 4
The expression of NR2F1 and NR2F2 in sagittal sections of the mouse brain at 1M (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data4-v1.zip
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Figure 1—source data 5
The expression of NR2F1 and NR2F2 in sagittal sections of the mouse brain at 1M (part 2); the Nissl staining results of the control and RXCre/+; Nr2f2F/F mutant mice at 1M (part 2).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data5-v1.zip
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Figure 1—source data 6
The expression of NR2F1 and NR2F2 in sagittal sections of the mouse brain at 1M (part 3); western blots data for the expression of NR2F1 and NR2F2 in the dorsal and ventral hippocampus at 1M; the Nissl staining results of the control and RXCre/+; Nr2f2F/F mutant mice at 1M (part 3).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-data6-v1.zip
Figure 1—figure supplement 1
The expression of Nr2f genes in the early developing hippocampus and different conditional knock mouse models.
(A) The expression of Nr2f1 and Nr2f2 genes in the forebrain at E10.5 (a, b) and E11.5 (c, d). (B) The expression of Nr2f1 and Nr2f2 genes in the developing hippocampus at E12.5 (a–c), E14.5 (d–f), …
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Figure 1—figure supplement 1—source data 1
The expression of Nr2f1 and Nr2f2 genes in the developing hippocampus at E12.5; the deletion efficiency of RXCre recombinase in the hippocampus of RXCre/+; Nr2f2F/F, RXCre/+; Nr2f1F/F, and RXCre/+; Nr2f1F/F; Nr2f2F/F mice (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-figsupp1-data1-v1.zip
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Figure 1—figure supplement 1—source data 2
The expression of Nr2f1 and Nr2f2 genes in the telencephalon at E10.5, E11.5, E14.5, and P0; the deletion efficiency of RXCre recombinase in the hippocampus of RXCre/+; Nr2f2F/F, RXCre/+; Nr2f1F/F, and RXCre/+; Nr2f1F/F; Nr2f2F/F mice (part 2).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig1-figsupp1-data2-v1.zip
Figure 2 with 1 supplement
The specification and differentiation of the dorsal CA1 lineage failed with the dysplastic dorsal hippocampus in RXCre/+; Nr2f1F/F mutant mice.
(A) In coronal sections along the rostrocaudal axis (a–f) and sagittal sections along the lateral–medial axis (g–l) of the hippocampus, compared with that of control mice (a–c, g–i), the dorsal …
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Figure 2—source data 1
The Nissl staining results of the control and RXCre/+; Nr2f1F/F mutant mice at 1M (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig2-data1-v1.zip
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Figure 2—source data 2
The Nissl staining results of the control and RXCre/+; Nr2f1F/F mutant mice at 1M (part 2); the expression of HuB and Wfs1 in the hippocampus of the control and RXCre/+; Nr2f1F/F mutant mice at 1M.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig2-data2-v1.zip
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Figure 2—source data 3
The expression of HuB and Ctip2 in the hippocampus of the control and RXCre/+; Nr2f1F/F mutant mice at 1M.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig2-data3-v1.zip
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Figure 2—source data 4
The expression of HuB, Wfs1, and Ctip2 in the hippocampus of the control and RXCre/+; Nr2f1F/F mutant mice at 1M.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig2-data4-v1.zip
Figure 2—figure supplement 1
Defects in Emx1Cre/+; Nr2f1F/F mutant mice.
(A) Immunofluorescence staining data showed that compared with those of control mice (a, c, e, g), the proportions of either the Wfs1- or Ctip2-positive dorsal CA1 domain were reduced in Emx1Cre/+; …
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Figure 2—figure supplement 1—source data 1
The expression of Wfs1 and Ctip2 in the dorsal hippocampus of the control and Emx1Cre/+; Nr2f1F/F mutant mice at 3M; Golgi staining results of the dorsal hippocampal CA1 pyramidal neurons and Morris water maze behavior test data of the control and Emx1Cre/+; Nr2f1F/F mutant mice.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig2-figsupp1-data1-v1.zip
Figure 3 with 1 supplement
Defects in the hippocampus in RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice.
(A) In coronal sections along the rostrocaudal axis, compared with control mice (a–d), the hippocampus was atrophic in RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice, indicated by the star, and an …
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Figure 3—source data 1
The Nissl staining results of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-data1-v1.zip
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Figure 3—source data 2
The expression of HuB and Ctip2 in the hippocampus of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-data2-v1.zip
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Figure 3—source data 3
The expression of HuB and Prox1 in the hippocampus of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-data3-v1.zip
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Figure 3—source data 4
The expression of HuB, Ctip2, and Prox1 in the hippocampus of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-data4-v1.zip
Figure 3—figure supplement 1
Adult neurogenesis was abnormal in the hippocampi of Nr2f1/2 double-gene mutant mice.
(A) The expression of GFAP and Nestin, markers of NSCs, in the SGZ of the vDG in control and Nr2f2 mutant mice at 1M (a–h), in the SGZ of the dDG in control and Nr2f1 mutant mice at 1M (i–p) and in …
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Figure 3—figure supplement 1—source data 1
The expression of GFAP, Nestin, and Dcx in the subgranular zone (SGZ) of ventral dentate gyrus (vDG) in the control and RXCre/+; Nr2f2F/F mutant mice at 1M, in the SGZ of dorsal dentate gyrus (dDG) in the control and RXCre/+; Nr2f1F/F mutant mice at 1M, and in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-figsupp1-data1-v1.zip
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Figure 3—figure supplement 1—source data 2
The expression of GFAP, Nestin, and Dcx in the subgranular zone (SGZ) of ventral dentate gyrus (vDG) in the control and RXCre/+; Nr2f2F/F mutant mice at 1M, in the SGZ of dorsal dentate gyrus (dDG) in the control and RXCre/+; Nr2f1F/F mutant mice at 1M, and in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W (part 2).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-figsupp1-data2-v1.zip
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Figure 3—figure supplement 1—source data 3
The expression of GFAP and Nestin in the subgranular zone (SGZ) of ventral dentate gyrus (vDG) in the control and RXCre/+; Nr2f2F/F mutant mice at 1M, in the SGZ of dorsal dentate gyrus (dDG) in the control and RXCre/+; Nr2f1F/F mutant mice at 1M, and in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W; quantitative analysis of GFAP/Nestin-positive cells in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-figsupp1-data3-v1.zip
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Figure 3—figure supplement 1—source data 4
The expression of GFAP, Nestin, and Dcx in the subgranular zone (SGZ) of ventral dentate gyrus (vDG) in the control and RXCre/+; Nr2f2F/F mutant mice at 1M, in the SGZ of dorsal dentate gyrus (dDG) in the control and RXCre/+; Nr2f1F/F mutant mice at 1M, and in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W (part 3); quantitative analysis of Dcx-positive cells in the SGZ of DG in the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig3-figsupp1-data4-v1.zip
Figure 4
The impairment of hippocampal trisynaptic connectivity in Nr2f2 single-gene, Nr2f1 single-gene, and Nr2f1/2 double-gene mutant mice.
(A) The expression of Calretinin, Calbindin, and SMI312 in the ventral hippocampus of the control (a, b, e, f, i, j) and Nr2f2 single-gene mutant mice (c, d, g, h, k, l). (B) The expression of …
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Figure 4—source data 1
The expression of Calretinin, Calbindin, and SMI312 in the ventral hippocampus of the control and RXCre/+; Nr2f2F/F single-gene mutant mice at 1M.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig4-data1-v1.zip
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Figure 4—source data 2
The expression SMI312 in the dorsal hippocampus of the control and RXCre/+; Nr2f1F/F single-gene mutant mice at 1M, and the expression of Calretinin and Calbindin in the hippocampus of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig4-data2-v1.zip
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Figure 4—source data 3
The expression of Calretinin and Calbindin in the dorsal hippocampus of the control and RXCre/+; Nr2f1F/F single-gene mutant mice at 1M, and the expression of SMI312 in the hippocampus of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-gene mutant mice at 3W.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig4-data3-v1.zip
Figure 5 with 1 supplement
Nr2f genes regulate the expression of key genes associated with early hippocampal development.
(A) The expression profiles of genes involved in hippocampal development in control and the double-mutant mice at E11.5. Data are presented as mean ± SEM. Student’s t test was used in A, *P<0.05, **P…
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Figure 5—source data 1
The expression of Lhx5 and Lhx2 in the telencephalon of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E14.5; the expression of Tbr2 and NeuroD1 in the telencephalon of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E14.5 (part 1).
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig5-data1-v1.zip
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Figure 5—source data 2
The expression of Sox2, Tbr2, and NeuroD1 in the telencephalon of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E14.5.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig5-data2-v1.zip
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Figure 5—source data 3
The expression profiles of genes involved in the hippocampal development of the control and double-mutant mice at E11.5; the expression of Lhx5 and Lhx2 in the telencephalon of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E11.5 and E13.5; the expression of Tbr2 and NeuroD1 in the telencephalon of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E14.5 (part 2); quantitative analysis of Tbr2-positive and NeuroD1-positive cells in the hippocampal primordium of the control and RXCre/+; Nr2f1F/F; Nr2f2F/F double-mutant mice at E14.5.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig5-data3-v1.zip
Figure 5—figure supplement 1
Nr2f1 and Nr2f2 genes coordinate to control distinct characteristics of the hippocampus.
Roles of Nr2f1 and Nr2f2 genes in the development and function of the hippocampus and the association with neurological diseases. Nr2f1 is required for the morphogenesis of the dorsal hippocampus …
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Figure 5—figure supplement 1—source data 1
Roles of Nr2f1 and Nr2f2 genes in the development and function of the hippocampus and the association with neurological disorders.
- https://cdn.elifesciences.org/articles/86940/elife-86940-fig5-figsupp1-data1-v1.zip
